2(substituted phenyl)-8h-pyrazolo-(5,1a)isoindol-8-one

ABSTRACT

Certain 8H-pyrazolo(5,1-a)isoindol-8-ones are effective plant growth modifiers.

United States Patent McKusick 1 Oct. 24, 1972 [5 2(SUBSTITUTEDPHENYL)-8H- PYRAZOLO-(S,1A)ISOINDOL-8-ONE [56] References Cited [72]Inventor: Blaine Chase McKusiclg, Wilming- UNITED STATES PA 3,409,42511/1968 Bousquet ..260/310 [73] Assignee: E. I. du Pont de Nemours andCompany, Wilmingt D L Primary Examiner-Henry R. Jiles AssistantExaminer-Harry I. Moatz [22] Flled: 1970 Attorney-Anthony P. Mentis 21 ALN 97030 1 pp 0 57] ABSTRACT Certain 8H-pyrazolo[5,l-a]isoindol-8-onesare effec- [52] U.S. Cl. ..260/310 R, 71/76 51 1m. 01. ..C07d 57/24plant gmwth [58] 5 Claims, No Drawings Field of Search ..260/310 1'2(SUBSTITUTED PHENYL} 8H-PYRAZOL0- (5,lA)ISOINDOL-8-ONE BACKGROUND OFTHE INVENTION (wherein R can include phenyl, halophen yli alkylphenyl,or alkoxyphenyl; R" can be H; R' can be H or halogen, and m is aninteger of up to 5) are plant growth regulants.

DESCRIPTION OF THE INVENTION The basic pyrazolo[5,l-a]isoindole ringsystem has been given the following numbering in the Ring Index:

The compounds of this invention have unsaturation at the 3 and 3a bond,an oxo group attached to the 8-position and nuclear carbon of a phenylgroup attached to the 2-position. At the 3-position hydrogen is presentand the 4, 5, 6, and 7-positions preferably have hydrogen on thisaromatic ring.

We have now obtained 8I-l-pyrazolo[5,1-a]isoindol- -ones of the formulawherein X, Y, and Z, alike or different, are H, alkyl of up to fourcarbon atoms, alkoxy of up to four carbon atoms, halogen, or nitro, andwith preferably at least two being hydrogen. These new compounds areuseful in controlling or regulating the growth of plants.

The new compounds are prepared by dehydrogenation of the corresponding3,3a-dihydropyrazolo[5,la]-isoindol-8-one. Althoughdichlorodicyanobenzoquinone is an effective agent, other oxidizingagents effective in solution are useful.

The 3,3a-dihydro compounds are available by the process of US. Pat. Nos.3,407,206 and 3,409,425. The reaction involves that of acetophenone or asubstituted acetophenone with phthalaldehydic acid in the presence of abase to give upon acidification, a 3- phenacylphthalide which is thenreacted with hydrazine as shown by the following equations:

The latter on oxidation gives the compounds The3,3a-dihydro-8I-I-pyrazolo[5,l-a]isoindol 8- ones are prepared in thefollowing manner. Phthalaldehydic acid is treated in the presence of abase with a ketone; i.e., acetophenone or substituted acetophenone.Generally, inert solvents such as ethanol, methanol, acetonitrile andbenzene are preferred for the reaction along with bases such aspotassium and sodium hydroxide. It is desirable to have more than oneequivalent of base.

The mixture is stirred for 1 to 6 hours at 20 to C, 25 to 35C beingpreferred. The reaction is essentially complete and is so indicated byprecipitation of the compound, by disappearance of the peak attributableto the aldehyde group in the infrared spectrum or by other appropriatemeans. The solution is diluted with water and acidified, usually withconcentrated hydrochloric acid, which completes the precipitation ofessentially pure 3-substituted phthalide. Further purification can beeffected by recrystallization from an appropriate solvent such asbenzene, acetonitrile or ethanol.

A mixture of the 3-substituted phthalide and hydrazine, usually as thehydrochloride, sulfate or hydrate, in an inert solvent such as aqueousethanol or methanol is heated to near reflux. It is desirable to use anexcess of one of the reactants. After a few minutes, an excess oftriethylamine is added gradually, and the mixture is heated at refluxfor l to 3 hours. The cooled solution is acidified, generally withhydrochloric acid benzene, acetonitrile, ethanol or nitromethane.

Examples of the preparation of representative 3,3adihydro-8H-pyrazolo[ 5l -a]isoindol-8-ones by the above general procedure are shown in Table1.

obtained TABLE I Substituted 3,3a- Su'bstituted Dihydropyrazolo Ex.KetonePhthalide [5, l-alisoindolones A 2'-chloro- 3-(o-chlorophena-2(o-chlorophenyl) acetophecyl)phthalide -3,3a-dihydro-8H- none pyrazolo[5,l-a]

isoindol-S-one B 2'-fluoro- 3-(o-fluorophena- 2-(o-fluorophenyl)-acetophecyl)phthalide 3,3a-dihydro-8H- none pyrazlo[5,l-a]

isoindol-S-one C 4'-bromo- 3-( p-bromophena- 2-(p-bromophenyl)-acetophecyhphthalide 3,3a-dihydro-8H- none pyrazolo [5,l-a]

isoindol-8-one D 4'-iodo- 3-( p-iodophena- 2-(p-iodophenyl)-acetophecyl)phthalide 3,3a-dihydro-8H- none pyrazolo[5,l-a]

isoindol8-one E 4'-butoxy- 3-(p-butoxyphena- 2-(p-butoxyphenyl)-acetophecyl)phthalide 3,3a-dihydro-8H- none pyrazolo [5,l-a]

isbindol-B-one F 3'-nitro- 3-(m-nitrophena-3,3a-dihydro-2-(macetophecyl)phthalide nitrophenyl)-8H- nonepyraz0lo[5,l-a]

isoindol-S-one G 3'. 4', 5'- 3-(3,4,5-trichloro- 3,3a-dihydro-2-(3,

trichlorophenacyllphthalide 4,5-trichloroacetophephenyl)-8H-pyrazononelo[5,l-a] isoindol- 8-one H 3 5 '-di- 3-( 3,5-di-tert- 2-(3,5-di-tert-buttert-butyl butylphenacyl) ylphenyl)-3,3a-

-acetophe- I phthalide dihydro-8H-pyralonone lo[5,l-a]-isoindol -8-one l3 ',4,5 3-( 3,4,5-trimethyl- 3 ,3a-dihydro-2-( 3,

trimethylphenacyl) phthalide 4,5-trimethylacetophephenyl)-8H-pyrazononelo[5,l-a]-isoindol -8-one The oxidizing agents include those effectivefor dehydrogenation of hydroaromatic compounds.

TABLE II Example Substituted Pyrazolo[ 5, Lafisoindolone2-(o-Chlorophenyl)-8H-pyrazolo[5,1-

a]isoindol-8 one 2-(o-Fluorophenyl)-8H-pyrazolo[5, l-

alisoindol-S-one Z-(p-Iodophenyl)-8l-l-pyrazolo[5,1-]isoindol 8one2-(m-Nitrophenyl)-8-H-pyrazolo[ 5 l a]isoindol-8-one 2-(3,4,5-Trichlorophenyl-8H-pyrazolo[5 l -a ]isoindol-8-one 2-( 3,5-Di-tert-butylphenyl)-8H-pyrazolo[5 l alisoindol-S-one 2-(3,4,5-Trimethylphenyl)-8H-pyrazolo[ 5 ,1-

a]isoindol-8-one SPECIFIC EMBODIMENTS OF THE INVENTION The following areillustrative examples in which al parts are by weight unless otherwisestated.

EXAMPLE 1 X=Z--H Y==OCH3 2j-( p-Methoxyphenyl)-8H-pyrazolo[ 5 l -aisoindo1e-8- one A 300 ml flask fitted with a nitrogen ebullator andreflux condenser was charged with 4.72 g (0.0216 mole) of2,3-dichloro-5,6-di-cyanobenzoquinone and 50 ml of benzene. The mixturewas warmed until a solution had formed, then a solution of 12 g (0.0432mole) of pyrazolo[5,l-a]isoindol-8-one in ml hot benzene was added allat once. The resulting mixture was refluxed for 3 hours, then anadditional 4.72 g (0.0216 mole) portion of2,3-dichloro-5,6-dicyanobenzoquinone was added and refluxing wascontinued for an additional 2.5 hours. The hot mixture was filtered bysuction and the precipitate was washed on the filter with a little hotbenzene. After air drying the precipitate, which was a deep orangecolored gritty solid, weighed 16.1 g and melted on a metal block at230-240C. Refluxing of the filtrate was resumed and continued overnightand an additional 1.1 g of product melting at 232240C was obtained.These products were combined, mixed vigorously with 200 ml H O, thenwith a solution of 5.6 g (0.1 mole) potassium hydroxide in 50 ml H O forone-half hour. The originally orange colored solid turned yellow. It wasfiltered, washed with water and air dried. It weighed 6.8 g and meltedat -l86C on a metal (Fisher) block. After crystallization from acetoneit melted at 186-l8 7C (yellow needle-shaped crystals).

Analysis:

Calculated for C, H N,O,: c, 73.9; H, 4.35; N, 10.14 Found: C, 73.68: H,4.55: N, 10.20

By concentration of the benzene filtrate from the above operation toabout 50 ml an additional 4.3 g product, melting at 185-186C, wasobtained.

3,3a-dihydro-2-(p-methoxyphenyl)-8H- By procedures essentially the sameas described for Example I the following three compounds were prepared:

Ex. Starting Pro- Compoundduct Analysis MPC Calcd for C H N 2-(2,l83-l84 4-xylyl)- 8H- Py 2010- [5,1- alisooindol- 8-one c i-i mo 78.835.11 10.22

Found: c lll IONIC 4 3,3a-dihl46-l47 11.39

ydro-2-phenly-SH -pyrazolo 5, 1 -21]- isoindol- 8-one 2-phenyl- 8H- [5.l a]- isoindol- -8-one Found: 78.06

EXAMPLE 5 An intimate mixture of 2.87 g (0.01 mole) of 3,3adihydro-2-(p-methoxyphenyl )-8H-pyrazolo[ 5, la]isoindol-8-one and 0.32 g (0.01gram atom) of powdered sulfur was placed in an 18 X 150 mm test tube.The vessel was placed in an oil bath heated at l94-l95 C. The mixturewhich gradually melted and which was stirred at frequent intervalscopiously liberated hydrogen sulfide for about 10 minutes. The vesselwas removed from the hot oil bath after about 25 minutes and aftercooling the product was pulverized by mixing under about 20 ml ofacetone. The acetone mixture was cooled to about l0, filtered, washedwith cold acetone and air dried to give 2.2 g of a yellow solid whichmelted at l40-l50C. Crystallization of this product from acetone yielded1.11 g of yellow crystals melting at l84-l85C on a metal (Fisher) blockand the melting point of this product in admixture with the product ofExample 1 was not depressed.

These new compounds are applied to the immediate area where the plant isdeveloping and growing. This includes pre-emergence and post-emergenceapplication.

Low rates of application of the active ingredient from 0.0025 to 8pounds per acre provides a means for regulating the growth of plants;e.g., growth retardation, epinasty, delayed flowering, preventing offruit set, carbohydrate enrichment and control of axillary growth. Athigher rates of application, from 10 to 40 pounds per acre, compounds ofthis invention exhibit herbicidal activity on some-plant species underspecific growth conditions. However, on other plant species thesecompounds are herbicidal at a rate of 2 pounds per acre or even lower.The compound is applied with conventional agricultural equipment. Theactual rate of active ingredient used, of course, must depend on theparticular situation, i.e., the actual plant species, its vigor, thetime of year and the condition of the soil.

The growth regulant compositions comprise a compound of this inventiongenerally with one or more surface-active agents.

The surface-active agent used in this invention can be a wetting,dispersing or an emulsifying agent which will assist dispersion of thecompound. The surface-active agent or surfactant can include suchanionic, cationic and nonionic agents as have heretofore been generallyemployed in plant control compositions of similar type. Suitablesurface-active agents are set out, for example, in Searle US. Pat. No.2,426,417; Todd US. Pat. No. 2,655,447; Jones US. Pat. No. 2,412,510; orLenher US. Pat. No. 2,139,276. A detailed list of such agents is setforth in Detergents and Emulsifiers Annual (1965) by John W. Mc-Cutcheon, Inc.

in general, less than 10 percent by weight of the surface-active agentswill be used in compositions of this invention and ordinarily the amountof surface-active agents will range from l-5 percent but may even beless than 1 percent by weight.

Plant growth regulant compositions can contain, in addition to asurfactant, finely divided inert diluents such as talcs, natural claysincluding atapulgite clay and kaolinite clay, pyrophyllite, diatomaceousearths, synthetic fine silicas, calcium silicate, carbonates, calciumphosphates, sulfur, lime and such flours as walnut shell, wheat,redwood, soybean and cottonseed.

The amount of the finely divided inert solid diluent can vary widely butwill generally range from 10 to 98 percent by weight of the growthretardant composition. The particle size can vary considerably but willordinarily be somewhat under 50 microns in the finished formulation.Such compositions are prepared by blending the ingredients and grindingin a hammer mill or an air attrition mill or similar device untiluniform powders are obtained which have a particle size smaller than 50microns. Compositions containing a surfaceactive agent and a solid inertdiluent are preferably wettable powders containing from 25 to percent ofpyrazoloisoindolone.

The pyrazoloisoindolones can also be formulated as high strengthcompositions in which the active ingredient can be present in amountsranging from 90-99 percent. The remainder of the composition comprisessurface-active agents, preferably in amounts of from 0.2 to 2 percentand diluents, as described above. Such compositions are prepared byblending and grinding the ingredients to obtain a homogeneous powder offine particle size.

Compositions of these plant growth regulants and inert solid diluentscan also be formulated into granules and pellets. In such compositions,the diluent will generally range from 65 to 99 percent and the activeingredient can range from 1 to 35 percent.

They can also be usedin the preparation of suspension concentrates,e.g., water extendable emulsifiable oil concentrates.

The compound of Example 4, 2-phenyl-8l-l-pyrazolo-[5,l-a]-isoindol-8-one, is an active pre-emergence herbicide at both l6and 2 lb. per acre. It inhibits the growth of crabgrass, sorghum,nutsedge, mustard and marigold whereas the corresponding 3,3a-dihydrocompound of U. S. Pat. No. 3,409,425 has practically no inhibitingefiect on the same plants.

At'an application of 2 lb. per acre the compound of Example 1 has astrong inhibiting efiect, post emergence, on Johnson grass and crabgrasswhereas the saturated analogue has a much weaker action. The compound ofExample 1 should not be used, however, where cotton is planted since itappears to have an undesirable effect on this plant.

The compound of Example 1 when applied as a preemergence plant growthregulator at a rate of 1 lb.

per acre as a soil mix has no effect on the growth of com. The saturatedanalogue, on the other hand, when applied under similar conditionsalmost kills corn.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:

l. A compound of the formula wherein Y X, Y and Z, alike or different,are hydrogen, alkyl of up to four, carbon atoms, OH, alkoxy of up tofour carbon atoms, halogen or nitro. 2. A compound according to claim lwherein X and Z are each hydrogen and Y is OCl-L.

3. A compound according to claim 1. wherein X and Y are each methyl andZ is hydrogen.

4. A compound according to claim 1 wherein X and Z are each hydrogen andY is OC,H i

5. A compound according to claim 1 wherein X, Y and Z are each hydrogen.

2. A compound according to claim 1 wherein X and Z are each hydrogEn andY is OCH3.
 3. A compound according to claim 1 wherein X and Y are eachmethyl and Z is hydrogen.
 4. A compound according to claim 1 wherein Xand Z are each hydrogen and Y is OC2H5.
 5. A compound according to claim1 wherein X, Y and Z are each hydrogen.